1) The document discusses the role of palbociclib, a CDK4/6 inhibitor, in the treatment of metastatic breast cancer.
2) Key clinical trials showed that combining palbociclib with an aromatase inhibitor significantly improved progression-free survival compared to an aromatase inhibitor alone.
3) The BOLERO-2 trial found that adding everolimus, an mTOR inhibitor, to exemestane improved progression-free survival by 5 months and overall survival by 6 months compared to exemestane alone in metastatic breast cancer.
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Pathology and Oncology Expert Perspectives in the Management of Triple-Negati...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Dr. Ira Bleiweiss, Chief of Breast Pathology at the University of Pennsylvania, and Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, will feature expert pathology and oncology perspectives on the management of triple-negative breast cancer (TNBC), including case explorations and insights into frequently asked questions. Register today to hear these expert perspectives!
Statement of Need
Triple-negative breast cancer (TNBC) is an aggressive disease that accounts for approximately 10% to 15% of breast cancer diagnoses and is characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). TNBC is more common in Black women and in women under the age of 40 (ACS, 2023). Compared with other subtypes of invasive breast cancer, TNBC has high rates of metastasis and a poor prognosis. Due to the lack of hormone and receptor targets, therapeutic options are limited, and prognostication and treatment selection are complicated by the heterogeneity of the disease (Yang et al, 2022). In this live webinar, Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and Dr. Ira Bleiweiss, Chief of Breast Pathology at the Hospital of the University of Pennsylvania, will provide expert oncology and pathology perspectives on evidence-based strategies for diagnosis, treatment, and adverse event management for patients with TNBC.
TARGET AUDIENCE
Medical oncologists, surgical oncologists, radiation oncologists, pathologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with triple-negative breast cancer (TNBC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate receptor and expression status for prognostication and treatment selection in TNBC
Differentiate the pathological characteristics of the various types of TNBC
Select optimal therapy for TNBC based on shared goals, biomarker testing, and clinical data on novel therapies
Discuss strategies for timely recognition and mitigation of adverse events associated with novel TNBC therapies
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
Presentation is highlighting the integration of different modalities in the management of locally advanced and metastatic prostate cancer pointing to the proven values of adding chemotherapy. A special note has been made to oligometastatic disease.
Kimberly Halla, MSN, FNP-C, Paula J. Anastasia, RN, MN, AOCN, and Nelli Zafman, MSN, CRNP, AOCNP prepared useful Practice Aids pertaining to PARP inhibitor therapy for this CNE activity titled, "Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses on the Advances and Challenges." For the full presentation, monograph, complete CNE information, and to apply for credit, please visit us at http://bit.ly/2EkO5Ij. CNE credit will be available until May 22, 2020.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Adjuvant Endocrine Therapy For Postmenopausal Breast CancerEmad Shash
Questions Covered in the presentation:
• Should patients receive an AI or Tamoxifen?
• Should patients receive monotherapy (AI or Tamoxifen alone) or sequential
therapy using both?
• 5 vs 10 years of therapy?
• If More than 5 years of endocrine therapy, which class to be used
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...Pharma Intelligence
In conjunction with a Key Opinion Leader, Dr. Peter Lee MD Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA, several Informa analysts discuss the major developments of the conference and key take-aways via a Webinar.
Watch our recording of Biomedtracker's Robert Jeng, Ph,D., Citeline's Allison Bruce, Scrip's Mary Jo Laffler, and Datamonitor Healthcare's Zachary McLellan as they download and debrief following the always-exciting ASCO weekend.
View and listen to the full webinar here https://www.youtube.com/watch?v=7yMsCb3R5X8
What’s the Latest in Clear Cell Ovarian Cancer?bkling
The understanding of clear cell ovarian cancer is evolving. If you’re diagnosed with clear cell ovarian cancer and eager for information specific to your subtype, we’ve got you covered! Join Dr. Jubilee Brown, Professor and Director of Gynecologic Oncology at Levine Cancer Institute, as she discusses current treatment options and any promising advances. Come with your questions and leave more informed about your subtype.
Pathology and Oncology Expert Perspectives in the Management of Triple-Negati...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck, presented by Dr. Ira Bleiweiss, Chief of Breast Pathology at the University of Pennsylvania, and Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, will feature expert pathology and oncology perspectives on the management of triple-negative breast cancer (TNBC), including case explorations and insights into frequently asked questions. Register today to hear these expert perspectives!
Statement of Need
Triple-negative breast cancer (TNBC) is an aggressive disease that accounts for approximately 10% to 15% of breast cancer diagnoses and is characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). TNBC is more common in Black women and in women under the age of 40 (ACS, 2023). Compared with other subtypes of invasive breast cancer, TNBC has high rates of metastasis and a poor prognosis. Due to the lack of hormone and receptor targets, therapeutic options are limited, and prognostication and treatment selection are complicated by the heterogeneity of the disease (Yang et al, 2022). In this live webinar, Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and Dr. Ira Bleiweiss, Chief of Breast Pathology at the Hospital of the University of Pennsylvania, will provide expert oncology and pathology perspectives on evidence-based strategies for diagnosis, treatment, and adverse event management for patients with TNBC.
TARGET AUDIENCE
Medical oncologists, surgical oncologists, radiation oncologists, pathologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with triple-negative breast cancer (TNBC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate receptor and expression status for prognostication and treatment selection in TNBC
Differentiate the pathological characteristics of the various types of TNBC
Select optimal therapy for TNBC based on shared goals, biomarker testing, and clinical data on novel therapies
Discuss strategies for timely recognition and mitigation of adverse events associated with novel TNBC therapies
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
Presentation is highlighting the integration of different modalities in the management of locally advanced and metastatic prostate cancer pointing to the proven values of adding chemotherapy. A special note has been made to oligometastatic disease.
Kimberly Halla, MSN, FNP-C, Paula J. Anastasia, RN, MN, AOCN, and Nelli Zafman, MSN, CRNP, AOCNP prepared useful Practice Aids pertaining to PARP inhibitor therapy for this CNE activity titled, "Realizing the Promise of PARP Inhibitors in Solid Tumor Therapy: Guiding Oncology Nurses on the Advances and Challenges." For the full presentation, monograph, complete CNE information, and to apply for credit, please visit us at http://bit.ly/2EkO5Ij. CNE credit will be available until May 22, 2020.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Adjuvant Endocrine Therapy For Postmenopausal Breast CancerEmad Shash
Questions Covered in the presentation:
• Should patients receive an AI or Tamoxifen?
• Should patients receive monotherapy (AI or Tamoxifen alone) or sequential
therapy using both?
• 5 vs 10 years of therapy?
• If More than 5 years of endocrine therapy, which class to be used
ADC’s - What Everyone with MBC Should Know about Antibody Drug Conjugatesbkling
Antibody drug conjugates (ADC’s), a novel class of anticancer agents, have been around for decades but recently great strides have been made in metastatic breast cancer. Next generation ADC’s, sometimes referred to as ' Trojan Horses' have shown promising efficacy in all subtypes of MBC. Join Dr. Erika Hamilton, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, and partner with Tennessee Oncology PLCC, as she presents an overview of ADC’s, biomarkers and clinical mapping, current treatment options, as well as the promising trials to keep an eye on. There will be time for your questions throughout the presentation.
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...Pharma Intelligence
In conjunction with a Key Opinion Leader, Dr. Peter Lee MD Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA, several Informa analysts discuss the major developments of the conference and key take-aways via a Webinar.
Watch our recording of Biomedtracker's Robert Jeng, Ph,D., Citeline's Allison Bruce, Scrip's Mary Jo Laffler, and Datamonitor Healthcare's Zachary McLellan as they download and debrief following the always-exciting ASCO weekend.
View and listen to the full webinar here https://www.youtube.com/watch?v=7yMsCb3R5X8
What’s the Latest in Clear Cell Ovarian Cancer?bkling
The understanding of clear cell ovarian cancer is evolving. If you’re diagnosed with clear cell ovarian cancer and eager for information specific to your subtype, we’ve got you covered! Join Dr. Jubilee Brown, Professor and Director of Gynecologic Oncology at Levine Cancer Institute, as she discusses current treatment options and any promising advances. Come with your questions and leave more informed about your subtype.
Dr. Olwen Hahn, medical oncologist at the University of Chicago Department of Medicine, discusses recent developments in MBC research and treatment. Joining her is Dionna Koval, a metastatic breast cancer patient advocate.
Novel Strategies for Attacking the Epidermal Growth Factor ReceptorOSUCCC - James
Novel Strategies for Attacking the Epidermal Growth Factor Receptor
David Carbone, MD PhD
Director, James Thoracic Center
The Ohio State University
Columbus, OH USA
What's the latest in breast cancer treatment and research? Erica Mayer, MD, MPH, a medical oncologist in the Susan F. Smith Center for Women's Cancers, shares the latest breast cancer news.
This presentation was originally given on Oct. 16, 2015, at the annual Young Women with Breast Cancer Forum, hosted by the Program for Young Women with Breast Cancer in the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, in Boston, Mass.
Learn more: http://www.susanfsmith.org
Learn about the latest research and treatment for ER+ breast cancer. Erica Mayer, MD, MPH, medical oncologist with the Susan F. Smith Center for Women's Cancers, discusses new clinical trials and treatment options for this subset of breast cancer patient.
This presentation was originally given on Oct. 17, 2015, at the Metastatic Breast Cancer Forum, hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, in Boston, Mass.
Learn more: http://www.susanfsmith.org
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Palbociclib in Metastatic Breast Cancer
1. Management of Metastatic Breast Cancer –
Understanding role of Palbociclib in Indian setting
Dr. Vibhay Pareek
Jupiter Hospital
2. • Disclosure: Few slides taken from Pfizer
• Conflict of Interest: None
3.
4.
5.
6.
7.
8.
9. Recommendations from the ESO-ESMO ABC-2 panel
• “Endocrine therapy is the preferred option for hormone receptor positive
disease, even in the presence of visceral disease, unless there is concern
or proof of endocrine resistance, or there is disease needing a fast
response”
• Level of evidence IA
• Votes: 100% yes, 29 voters (of 43 members)
Cardoso F et al, The Breast 23:489 – 502, 2014, and Ann Oncol 2014
14. EVE 10 mg daily
+
EXE 25 mg daily (n = 485)
Placebo
+
EXE 25 mg daily (n = 239)
R
2:1
N = 724
•Postmenopausal ER+
•Unresectable locally
advanced or metastatic BC
•Recurrence or progression
after letrozole or anastrozole
The BOLERO-2 Phase III trial:
Everolimus in advanced disease
Baselga J, et al. N Engl J Med. 366:520-529, 2012
• 84% of patients sensitive to prior endocrine therapy (i.e. DFI > 24 mos. if relapse
while/after adjuvant AI or clinical benefit to the prior line of endocrine therapy for
advanced disease)
• 84% of patients received the study drugs as ≥ 2° line of therapy for advanced disease
15. The progression free survival improved by 5 months
with addition of everolimus to exemestane and
overall survival improved by 6 months
16. Safety profile everolimus:
most common adverse events
Adverse event Everolimus
N = 482
% G3-G4 (%G1-G4)
Placebo
N = 238
% G3-G4 (%G1-G4)
Stomatitis 8 (56) 1 (11)
Anemia 6 (16) 1 (4)
Dyspnea 4 (18) 1 (9)
Hyperglicemia 4 (13) 1 (2)
Fatigue 4 (33) 1 (26)
Pneumonitis 3 (12) - (-)
Baselga J et al, New Engl J Med 366: 520-9, 2012.
17. The TAMRAD trial
Bachelot T et al, J Clin Oncol 30: 2718-24, 2012
TAM TAM + Everolimus
Clinical benefit
rate at six months
42%
(95% CI: 29-56%)
61%
(95% CI: 47-74%)
• post-menopausal
• ER+/HER-2 neg No. = 111 pts.
• pre-treatment with AI
TAM + Everolimus
TAM
18. Changing paradigms with CDK 4/6
kinase inhibitors in ER+ HER2 – metastatic
breast cancer:
ROLE OF PALBOCICLIB
19. Metastatic Breast Cancer (MBC) Landscape
19
HER2+
Triple negative
~15%5
HER=human epidermal growth factor receptor; HR+=hormone receptor-positive.
1. Early Breast Cancer Trialists’ Collaborative Group, et al. Lancet. 2015;386:1341-1352. 2. O’Shaughnessy J. Oncologist. 2005;10(suppl 3):20-29.
3. National Cancer Institute. SEER cancer statistics review (CSR) 1975-2012. http://seer.cancer.gov/csr/1975_2012/. Accessed April 19, 2016. 4. Mayer M,
Grober SE. Silent voices: women with advanced (metastatic) breast cancer share their needs and preferences for information, support, and practical resources.
https://www.researchgate.net/publication/274510595_Silent_Voices_Women_with_Advanced_Metastatic_ Breast_Cancer_Share_
Their_Needs_and_Preferences_for_Information_Support_and_Practical_Resources. Accessed April 19, 2016.
5. Howlader N, et al. J Natl Cancer Inst. 2014;106(5):dju055.
Women
living with MBC4
HR+
HR+/HER2-
~61%5
HR+/HER2+
~15%5
HR-/HER2+
~9%5
Roughly 20% to 30% of women
who have had early disease will
develop advanced or metastatic
disease1,2
4% to 9% of all women with breast
cancer present with metastatic
disease at the
time of initial diagnosis3
20. Cyclin D1 and CDK4/6 Are Critical for Cellular
Proliferation
CDKs are key regulators of sequential progression through the G1, S, G2, and
M phases of the cell cycle
Dickson MA, Schwartz GK. Curr Oncol 2009;16:36–43
Shapiro GI. J Clin Oncol 2006;24:1770–83
M G1
G2 S
CDK4/6
Cyclin
D1/D2/D3
CDK2Cyclin A
CDK2Cyclin E
CDK1 Cyclin A
CDK1 Cyclin B
21. Cyclin D1 and CDK4/6 Are Downstream of Signaling Pathways That Lead
to Cellular Proliferation and regulate the G1-S checkpoint
Lange et al. Endocrine-Related Cancer 2011;18:C19–C24
RB
RB
Gene
transcriptionG2 S
M
G1
G0
P
P P
P
Inactive
Active tumor
suppressor
E2F
E2F
R
CDK4/6Cyclin D
Pl3K/Akt
STATs MAPKs
(ER/PR/AR) Wnt/β-catenin
NF-κB
p16
p21
p53
R = restriction point
RB- retinoblastoma gene product
E2F- transcription factors
22. 22
The Potential of Combined Targeting of ER and CDK4/6
• The complex, interconnected, and redundant
cellular pathways that are co-opted by cancer,
influence the therapeutic vulnerability of tumor
cells1
• Targeting multiple components within the ER
pathway may yield an enhanced effect1-3
– Upstream targeting of ER signaling may
decrease mitogenic signaling3
– Downstream targeting of CDK4/6 can cause cell
cycle arrest4
1. Osborne CK, et al. Annu Rev Med. 2011;62:233-247; 2. Yap TA, et al. J Clin Oncol. 2013;31:1592-1605;
3. Finn RS, et al. Breast Cancer Res. 2009;11:R77; 4. Finn RS, et al. Additional file;
http://www.biomedcentral.com/content/supplementary/bcr2419-S5.PPT. Accessed January 31, 2016;
5. Lange CA, et al. Endocr Relat Cancer. 2011;18:C19-C24; 6. Baselga J. Oncologist. 2011;16(suppl 1):12-19;
7. Asghar U, et al. Nat Rev Drug Discov. 2015;14:130-146;
8. VanArsdale T, et al. Clin Cancer Res. 2015;doi:10.1158/1078-0432.
NUCLEUS
CYTOPLASM
EXTRACELLULAR
SPACE
Growth
factor6
PI3K6
Receptor tyrosine
kinase6
Akt6
mTOR6
Estrogen1
ER1
pRb7
E2F7
Cellular proliferation7
Cyclin D1 +
CDK4/65-8
M
G18
S
G2
23. 23
NN O
N
NH
O
N
N
N
H2
+
S
O
O
O
OH
First-in-class CDK4/6 Inhibitor: Palbociclib
• Orally active selective inhibitor of CDK4 and CDK61,2
• Inhibits cell proliferation and cellular DNA synthesis by preventing
cell-cycle progression from G1 to S phase1
1. Fry DW, et al. Mol Cancer Ther 2004;3:1427–38
2. Menu E, et al. Cancer Res 2008;68:5519–23
3. Sutherland RL, Musgrove EA. Breast Cancer Res 2009;11:112
4. Van Arsdale T, et al. Clin Cancer Res 2015; Epub May 2
• Low nanomolar concentrations block
Rb phosphorylation, inducing specific G1
arrest in sensitive cell lines1-3
• Inhibits proliferation in cultured and
xenografted leukemia, myeloma, breast
cancer, colon cancer, and lung cancer
cells4
Palbociclib
(PD-0332991)
24.
25. 26
• Luminal, ER+ or HER2-amplified breast cancer cell lines most sensitive to CDK4/6 inhibition of
proliferation (non-luminal resistant)
• Synergistic growth inhibitory activity between palbociclib and tamoxifen (ER+) or trastuzumab
(HER2+)
• Palbociclib activity seen in acquired tamoxifen resistance
Palbociclib Preferentially Inhibits Proliferation of Luminal
ER+ Human Breast Cancer Cell Lines In Vitro
Finn RS, et al. Breast Cancer Res 2009;11:R77EMT, epithelial mesenchymal transition 26
0
100
200
300
400
500
600
700
800
900
1000
Luminal
HER2-amplified
Immortalized
Non-luminal/post EMT
Non-luminal
26. Combination Palbociclib and an Endocrine Therapy in
Preclinical Models
• In these preclinical analyses, treatment of breast cancer cell lines with the combination of palbociclib and an
endocrine therapy led to increased growth arrest compared to treatment with each drug alone2
CIm=mean combination index; ER=estrogen receptor; ET=endocrine therapy; nM=nanomolar; PAL=palbociclib.
1. Finn RS, et al. Breast Cancer Res. 2009;11(5):R77. 2. IBRANCE® Prescribing Information. New York, NY: Pfizer Inc; 2016.
0
80
60
40
20
100
T47D1
CIm=0.1 ± 0.01
6255000ET
PAL
Concentration (nM)
2500 1250 312
25 12.5 3.1256.2550
EFM191
0
80
60
40
20
100
6255000ET
PAL
Concentration (nM)
2500 1250 312
25 12.5 3.1256.2550
CIm=0.45 ± 0.09
0
80
60
40
20
100
62510,000ET
PAL
Concentration (nM)
2500 12505000 312
25 12.550 3.1256.25100
CIm=0.37 ± 0.04
MCF71
%Inhibition
Endocrine Therapy Alone Palbociclib + Endocrine Therapy CombinationPalbociclib Alone
27
• Preclinical analyses contributed to the rationale to combine IBRANCE with letrozole or fulvestrant in the PALOMA-1 and PALOMA-3 trials
• MCF7, EFM19, and T47D are ER+, estrogen-sensitive breast cancer cell lines that were treated with endocrine therapy alone, palbociclib
alone, or palbociclib + endocrine therapy over a range of concentrations; growth of the cell lines was measured1
27. 28
Dose ranging study: 3/1 Schedule Associated With
Prolonged SD vs 2/1 Schedule but Both Well Tolerated
1. Flaherty KT, et al. Clin Cancer Res 2012;18:568–76
2. Schwartz GK, et al. Br J Cancer 2011;104:1862–8
•Both schedules generally well tolerated
•2/1: 18% of patients had DLTs
•3/1: 12% of patients had DLTs
•Hematologic AEs: neutropenia/other cytopenias
•Most common non-hematologic AE: fatigue
•No treatment-related, grade 4/5 adverse events were reported
Primary endpoint:
safety1,2
•Prolonged SD with 3/1 schedule
•2/1: 6 patients (19%) achieved SD for ≥4 cycles, 3 (10%) for ≥10
cycles
•3/1: 10 patients (27%) achieved SD for ≥4 cycles, 6 (16%) for
≥10 cycles
Secondary
endpoint:
preliminary
antitumor efficacy1,2
•Dose-proportional exposure
•Slow absorption and elimination
•Large volume of distribution
Secondary
endpoint: PK of
palbociclib1,2
28. Once-Daily Oral Dosing With Palbociclib
29
Palbociclib® Prescribing Information
Palbociclib should be taken with food. Patients should be encouraged to take their dose at
approximately the same time each day
If the patient vomits or misses a dose, an additional dose should not be taken that day. The next
prescribed dose should be taken at the usual time
Palbociclib capsules should be swallowed whole (patients should not chew, crush, or open them prior to
swallowing). Capsules should not be ingested if they are broken, cracked, or otherwise not intact
Letrozole
2.5 mg
CONTINUOUS
ONCE-DAILY
DOSINGPO
Palbociclib
125 mg
3 WEEKS ON
1 WEEK OFFonce
daily
29. PALOMA 1/TRIO 18: Phase II Study Design in Patients with ER+,
HER2– Locally Recurrent or Metastatic Breast Cancer
Finn RS, et al. Lancet Oncol. 2015; 16(1): 25–35.
*Patients receiving letrozole alone did not cross over to the combination at the time of progression.
Adapted from Finn RS, et al. 2015.1
• Randomized phase II open-
label trial at 50 centers in 12
countries (NCT00721409)
• Key eligibility criteria:
inoperable locally recurrent
disease, postmenopausal
status, no prior therapy for
advanced breast cancer, no
prior CDK inhibitors, no
letrozole within 12 months,
no prior/current brain
metastases, measurable
disease (RECIST 1.0) or bone-
only disease, ECOG PS ≤1,
adequate bone marrow and
renal function
30. 31
PALOMA 1/TRIO 18: Progression-Free Survival (ITTP)
PAL + LET
(N=84)
LET
(N=81)
Number of Events (%) 41 (49) 59 (73)
Median PFS, months
(95% CI)
20.2
(13.8, 27.5)
10.2
(5.7, 12.6)
Hazard Ratio
(95% CI)
0.488
(0.319, 0.748)
P value 0.0004
90
80
70
60
50
40
30
20
10
0
Progressionfreesurvivalprobability(%)
0 4 8 12 16 20 24 28 32 36 40
Time (months)
84 67 60 47 36 28 21 13 8 5 1
81 48 36 28 19 14 6 3 3 1
PAL + LET
LET
Number of patients at risk
100
Palbociclib plus letrozole
Letrozole
Finn RS, et al. Lancet Oncol 2015;16:25-35
Reduction in the risk of
disease progression
with first-line
Palbociclib + letrozole
vs letrozole alone
51%
31. 32
PALOMA 1/TRIO 18: Best Overall Response
Finn RS, et al. Lancet Oncol 2015;16:25-35
Characteristic Combined Cohorts
PAL + LET LET
All randomized patients, n 84 81
Objective response rate, % (95% CI) 43 (32−54) 33 (23−45)
Complete response, n (%) 1 (1) 1 (1)
Partial response, n (%) 35 (42) 26 (32)
Stable disease, n (%) 37 (44) 30 (37)
Stable disease ≥24 weeks, n (%) 32 (38) 20 (25)
Stable disease <24 weeks, n (%) 5 (6) 10 (12)
Progressive disease, n (%) 3 (4) 18 (22)
Indeterminate, n (%) 8 (10) 6 (7)
Patients with measurable disease, n 65 66
Objective response rate, % (95% CI) 55 (43−68) 39 (28−52)
Complete response, n (%) 1 (2) 0
Partial response, n (%) 35 (54) 26 (39)
Stable disease, n (%) 20 (31) 22 (33)
Progressive disease, n (%) 2 (3) 15 (23)
Indeterminate, n (%) 7 (11) 3 (5)
33. 34
PALOMA 1/TRIO 18: Conclusions
• PALOMA-1 demonstrated the activity and safety of CDK 4/6 inhibition in the first-line setting in
patients with ER+/HER2- advanced breast cancer1
– Palbociclib + letrozole significantly prolonged PFS, irrespective of cyclin D1 and p16 alterations
– ORR and CBR were also substantially improved, confirming the clinical benefit
– OS data is immature at this time; a final OS analysis will be conducted following additional events
• Palbociclib + letrozole had a clinically manageable toxicity profile1
– The most common adverse event was uncomplicated neutropenia
• For patients with disease progression after study treatment, addition of palbociclib to letrozole did
not compromise the ability to receive further endocrine therapy or chemotherapy, and delayed the
start of subsequent therapy2
1. Finn RS, et al. Lancet Oncol 2015;16:25-35; 2. Finn RS et al.
Presented at SABCS 2015; San Antonio, Texas, USA (Poster 4-13-02)
34. 35
PALOMA-2: Phase III Study Design in Postmenopausal Patients with ER+, HER2–
Advanced Breast Cancer
clinicaltrials.gov NCT01740427;
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
35. PALOMA-2: Demographics and Baseline Characteristics
aVisceral disease was defined as: any lung (including pleura) and/or liver involvement bTime since completion of (neo)adjuvant therapy and onset of recurrence; percentage calculated based on number of
patients who received (neo)adjuvant therapy Patients who progressed while receiving or ≤12 months from completion of prior anastrozole or letrozole were excluded cPatients who received anastrozole or
letrozole as a component of their adjuvant or neoadjuvant therapy were excluded from the study if they had disease progression while receiving the therapy or within 12 months after completing the
therapyHormonal therapy included tamoxifen, anastrozole, letrozole, exemestane, goserelin, toremifene, other agents
Palbociclib + letrozole (N=444) Placebo + letrozole (N=222)
Age, n (%)
Median (range) 62 (30–89) 61 (28–88)
<65 years 263 (59.2) 141 (63.5)
65 years 181 (40.8) 81 (36.5)
ECOG PS, n (%)
0 257 (57.9) 102 (45.9)
1 178 (40.1) 117 (52.7)
2 9 (2.0) 3 (1.4)
Disease site, n (%)
Viscerala 214 (48.2) 110 (49.5)
Non-visceral 230 (51.8) 112 (50.5)
Bone-only 103 (23.2) 48 (21.6)
No. of disease sites
1 138 (31.1) 66 (29.7)
2 117 (26.4) 52 (23.4)
3 112 (25.2) 61 (27.5)
≥4 77 (17.3) 43 (19.4)
Disease-free interval,b n (%)
Newly metastatic disease 167 (37.6) 81 (36.5)
12 months 99 (22.3) 48 (21.6)
>12 months 178 (40.1) 93 (41.9)
Recurrence type, n (%)
Locoregional 2 (0.5) 2 (0.9)
Loca 6 (1.4) 3 (1.4)
Regional 3 (0.7) 1 (0.5)
Distant 294 (66.2) 145 (65.3)
Newly diasgnosed 139 (31.3) 71 (32.0)
Prior neoadjuvant therapy, n (%)
Chemotherapy 213 (48.0) 109 (49.1)
Adjuvant hormonal therapyc 249 (56.1) 126 (56.8)
36. 37
PALOMA-2: Investigator-assessed PFS (ITT Population)
• As initial therapy for postmenopausal ER+/HER2– advanced breast cancer, palbociclib + letrozole significantly
improved PFS compared with placebo + letrozole
CI, confidence interval; ER+, estrogen receptor;-positive HER2–, human epidermal growth factor receptor 2-
negative; HR, hazard ratio; ITT, intention to treat; LET, letrozole; NE, not estimable; PAL, palbociclib; PCB,
placebo; PFS, progression-free survival
PFSprobability(%)
Time from randomization (months)
0 3 6 9 12 15 18 21 24 27 30 33
444 395 360 328 295 263 238 154 69 29 10 2
222 171 148 131 116 98 81 54 22 12 4 2
PAL+LET
PCB+LET
Number of patients at risk
HR 0.58 (95% CI 0.46, 0.72)
2-sided P<0.001
Palbociclib + letrozole (n=444)
Placebo + letrozole (n=222)
Median (95% CI) PFS
14.5 months (12.9–17.1)
Median (95% CI) PFS
24.8 months (22.1–NE)
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
0
10
20
30
40
50
60
70
80
90
100
37. PALOMA-2: PFS Subgroup Analysis
• The PFS advantage for palbociclib + letrozole over letrozole alone was consistent across subgroups
aVisceral disease was defined as: any lung (including pleura) and/or liver involvement
CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group
Performance Status; HR, hazard ratio; ITT, intention to treat; LET, letrozole;
PAL, palbociclib; PCB, placebo; PFS, progression-free survival
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
Subgroup
Palbociclib–Letrozole,
n (%)
Placebo–Letrozole,
n (%)
HR (95% CI)
All randomized patients 444 (100) 222 (100) 0.58 (0.46–0.72)
Age <65 years
≥65 years
263 (59.2)
181 (40.8)
141 (63.5)
81 (36.5)
0.57 (0.43–0.74)
0.57 (0.39–0.84)
Race White
Asian
344 (77.5)
65 (14.6)
172 (77.5)
30 (13.5)
0.58 (0.45–0.74)
0.48 (0.27–0.87)
Site of metastatic disease Viscerala
Non-visceral
214 (48.2)
230 (51.8)
110 (49.5)
112 (50.5)
0.63 (0.47–0.85)
0.50 (0.36–0.70)
Prior hormonal therapy Yes
No
249 (56.1)
195 (43.9)
126 (56.8)
96 (43.2)
0.53 (0.40–0.70)
0.63 (0.44–0.90)
Disease-free interval Newly metastatic disease
≤12 months
>12 months
167 (37.6)
99 (22.3)
178 (40.1)
81 (36.5)
48 (21.6)
93 (41.9)
0.67 (0.46–0.99)
0.50 (0.33–0.76)
0.52 (0.37–0.73)
Region North America
Europe
Asia/Pacific
168 (37.8)
212 (47.7)
64 (14.4)
99 (44.6)
95 (42.8)
28 (12.6)
0.61 (0.43–0.85)
0.57 (0.41–0.80)
0.49 (0.27–0.87)
ECOG performance status 0
1/2
257 (57.9)
187 (42.1)
102 (45.9)
120 (54.1)
0.65 (0.47–0.90)
0.53 (0.39–0.72)
Bone-only disease at baseline Yes
No
103 (23.2)
341 (76.8)
48 (21.6)
174 (78.4)
0.36 (0.22–0.59)
0.65 (0.51–0.84)
Measurable disease Yes
No
338 (76.1)
106 (23.9)
171 (77.0)
51 (23.0)
0.66 (0.52–0.85)
0.35 (0.22–0.57)
Prior chemotherapy Yes
No
213 (48.0)
231 (52.0)
109 (49.1)
113 (50.9)
0.53 (0.40–0.72)
0.61 (0.44–0.84)
Most recent therapy Aromatase inhibitor
Antiestrogen
91 (20.5)
154 (34.7)
44 (19.8)
75 (33.8)
0.55 (0.34–0.88)
0.56 (0.39–0.80)
Number of disease sites 1
≥2
138 (31.1)
306 (68.9)
66 (29.7)
156 (70.3)
0.51 (0.34–0.77)
0.61 (0.47–0.79)
Histopathological classification Ductal carcinoma
Lobular carcinoma
356 (80.2)
68 (15.3)
184 (82.9)
30 (13.5)
0.59 (0.46–0.75)
0.46 (0.27–0.78)
In favor of PAL + LET In favor of PCB + LET
0.2 0.4 0.6 0.8 1.00 2.00
38. 39
PALOMA-2: Overall Response (ITT population)
• As initial therapy for postmenopausal ER+/HER2– advanced breast cancer, palbociclib + letrozole
improves ORR and CBR over letrozole alone
aConfirmed complete response + partial response.
bConfirmed complete response + partial response + stable disease ≥24 weeks.
COne patient with bone-only disease at baseline was included; all other patients had measurable disease at baseline
CI, confidence interval; CBR, clinical benefit rate; DoR, duration of response ER+, estrogen receptor-positive; HER2–, human epidermal growth factor receptor 2-
negative; ITT, intention to treat; NR, not reported; NS, not significant; ORR, overall response rate
Palbociclib +
letrozole
(N=444)
Placebo +
letrozole
(N=222)
Odds Ratio
(95% CI)
2-Sided
P Value
(Exact)
All randomized patients, n 444 222
ORR,a % (95% CI)
42.1
(37.5–46.9)
34.7
(28.4–41.3)
1.40
(0.98–2.01)
0.06
CBR,b % (95% CI)
84.9
(81.2–88.1)
70.3
(63.8–76.2)
2.39
(1.58–3.59)
<0.0001
Median DoR, mo 22.5
(19.8–28.0)
16.8c
(14.2–28.5)
NR NR
Patients with measurable disease 338 171
ORR,a % (95% CI)
55.3
(49.9–60.7)
44.4
(36.9–52.2)
1.55
(1.05–2.28)
0.03
CBR,b % (95% CI)
84.3
(80.0–88.0)
70.8
(63.3–77.5)
2.23
(1.39–3.56)
<0.001
Median DoR, mo
22.5
(19.8–28.0)
16.8
(15.4–28.5)
NR NR
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
39. 40
PALOMA-2: All-causality Hematological AEs occurring in ≥15% of patients in either arm
(as-treated population)
aIncludes clustered Medical Dictionary for Regulatory Activity (MedDRA) preferred terms.
AE, adverse event
Palbociclib + letrozole
(N=444)
Placebo + letrozole
(N=222)
Any grade Grade 3 Grade 4 Any grade Grade 3 Grade 4
Any AE, % 98.9 62.2 13.5 95.5 22.1 2.3
Neutropeniaa 79.5 56.1 10.4 6.3 0.9 0.5
Leukopeniaa 39.0 24.1 0.7 2.3 0 0
Anemiaa 24.1 5.2 0.2 9.0 1.8 0
Thrombocytopeniaa 15.5 1.4 0.2 1.4 0 0
• Grade 3/4 febrile neutropenia was reported in 1.8% of patients in the palbociclib + letrozole arm vs. 0% in the
placebo + letrozole arm
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
40. 41
Palbociclib + letrozole
(N=444)
Placebo + letrozole
(N=222)
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Any AE (%) 98.9 62.2 13.5 95.5 22.1 2.3
Fatigue 37.4 1.8 0 27.5 0.5 0
Nausea 35.1 0.2 0 26.1 1.8 0
Arthralgia 33.3 0.2 0 33.8 0.5 0
Alopeciaa 32.9 0 0 15.8 0 0
Diarrhea 26.1 1.4 0 19.4 1.4 0
Cough 25.0 0 0 18.9 0 0
Back pain 21.6 1.4 0 21.6 0 0
Headache 21.4 0.2 0 26.1 1.8 0
Hot flush 20.9 0 0 30.6 0 0
Constipation 19.4 0.5 0 15.3 0.5 0
Rashb 17.8 0.9 0 11.7 0.5 0
Asthenia 16.9 2.3 0 11.7 0 0
Vomiting 15.5 0.5 0 16.7 1.4 0
Pain in extremity 15.3 0.2 0 17.6 1.4 0
Stomatitis 15.3 0.2 0 5.9 0 0
PALOMA-2: All-causality Non-Hematological AEs Occurring in
≥15% of Patients
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
aIn the palbociclib + letrozole group, 30% patients had grade 1 alopecia and 3% had grade 2 alopecia. In the placebo +
letrozole group, 15% patients had grade 1 alopecia and 1% had grade 2 alopecia. bincludes MedRA preferred terms for
Rash. AE, adverse event
41. 42
PALOMA-2: Summary of AEs
SAEs
• Overall incidence of SAEs was higher in patients receiving palbociclib + letrozole vs. placebo +
letrozole (20% vs. 13%)
• SAEs were reported for <1% of patients in either treatment arm except febrile neutropenia (1.6%
palbociclib + letrozole arm vs. 0% placebo + letrozole arm) and pulmonary embolism (0.9%
palbociclib arm vs. 1.4% placebo arm)
Permanent treatment discontinuations of palbociclib or placebo associated with AEs
• 7% of patients in the palbociclib arm vs. 5% in the placebo arm
Deaths due to AEs
• 2.3% of patients in the palbociclib + letrozole arm vs. 1.8% in the placebo + letrozole arm
• One on-study death (secondary to lower respiratory tract infection and pulmonary embolism) in
the placebo + letrozole arm was considered treatment-related by the investigator
AE, adverse event; SAE, serious adverse event
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
42. 43
PALOMA-2: Conclusions
• Palbociclib combined with letrozole significantly improved median PFS compared with placebo + letrozole as first-
line therapy in women with
ER+/HER2– advanced breast cancer
– >10 month improvement in median PFS was observed (24.8 vs. 14.5 months)
– HR=0.58 (95% CI: 0.46–0.72; 2-sided P<0.001)
• Clinical benefit from palbociclib was also demonstrated across all
prespecified subgroups
• Palbociclib was well tolerated with the most common AEs being neutropenia and leukopenia; however, the overall
incidence of neutropenic fever was low (1.6%)
• PALOMA-2, a double-blind, placebo-controlled phase 3 trial confirmed the safety and efficacy of palbociclib +
letrozole demonstrated in the open-label phase 2 PALOMA-1 trial and builds on the efficacy and safety profile of
CDK 4/6 inhibition in the first-line treatment of advanced ER+/HER2– breast cancer
AE, adverse event; CI, confidence interval; ER+, estrogen receptor-positive;
HER2–, human epidermal growth factor receptor 2-negative; HR, hazard ratio;
PFS, progression-free survival
Finn RS, et al. N Engl J Med 2016 Nov 17;375(20): 1925–1936
48. 49
Chemotherapy-induced Neutropenia (CIN) Is Common,
Severe, and Associated with Fever, Infection, and Death
1. Crawford J, et al. Cancer. 2004;100:228−37
2. Eskander RN, Tewari KS. J Hematol Malig. 2012;2:63−73
3. Lalami Y, et al. Ann Oncol. 2006;17:507−14
4. Lyman GH, et al. Crit Rev Oncol Hematol. 2014;90:190−9
5. Pettengell R, et al. Support Care Cancer. 2008;16:1299−309
6. Kurkjian C, Ozer H. Chapter 157. In: DeVita V, et al, eds. Cancer. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:2300−13
7. Caggiano V, et al. Cancer. 2005;103:1916−24
8. Freifeld AG, et al. Clin Infect Dis. 2011;52:e56−e93
9. Kuderer N, et al. Cancer. 2006;106:2258−66
Characteristic Grade 3/4 Chemotherapy-induced Neutropenia (CIN)
Incidence Common
16-90% of adjuvant breast cancer patients;
>70% in advanced breast cancer patients1,2
Severity Severe to life-threatening
64% grade 3/4, 34% grade 4
in adjuvant/neo-adjuvant breast cancer patients5
Nadir Usually early, may be late ~1-2 weeks, delayed with some regimens6
Duration May be prolonged ~7-10 days, extended with some regimens6,7
FN incidence Common 10-50% of solid tumor patients1,3,8
Documented
infections
Common 20-30% of febrile neutropenia episodes8
FN mortality Common ~9% in solid tumor patients3,5,9
FN = febrile neutropenia
49. Palbociclib-induced Neutropenia (PIN) is Rapidly Reversible
1. Finn RS, et al. ESMO 2014 (Abstract 368P); 2. Finn RS, et al.
Lancet Oncol. 2015;16:25-35; 3. DeMichele A, et al. ASCO 2014 (Abstract 2547);
4. Turner N, et al. N Engl J Med 2015;373:209-19; 5. Cristofanilli M, et al. Lancet Oncol 2016
[Published online 2 March 2016; http://dx.doi.org/10.1016/S1470-2045(15)00613-0].
Incidence of neutropenia in patients on palbociclib in 3 phase II trials and 1 phase III trial
Incidence: Frequent1-3
Severity: Grade 3 common, grade 4 uncommon1-3
Nadir: Weeks 3-41,3
Duration: 7 days1
Febrile
neutropenia:
In PALOMA-1, no cases of febrile neutropenia were observed;1 in PALOMA-3, incidence with
palbociclib + fulvestrant (1.0%) was the same as placebo + fulvestrant (1.0%)5
Infections:
PALOMA-3 had more cases of neutropenia than PALOMA-1;2,4,5 incidence of infections in
PALOMA-3 was greater with palbociclib + fulvestrant than with placebo + fulvestrant, but most
were grade 1 or 2 severity4,5
Reversibility: Rapidly reversible with dose reduction, interruption, delay1
50
*All-causality events; patients received letrozole in addition to palbociclib †Causality of events not specified ‡All-causality events; patients received
fulvestrant in addition to palbociclib
Study
Number of
patients
All grades
(%)
Grade 3 (%) Grade 4 (%)
Grade 3/4
(%)
Finn et al1,2* 83 74 48 6 54
DeMichele et al3† 143 82 37.1 3.5 41
Turner et al.4‡ 347 78.8 53.3 8.7 62.0
Cristofanilli et al.5‡ 347 81 55 10 65
50.
51. Proactively Monitor Patients to Help Manage Potential
Side Effects
52
Monitor CBC prior to the start of Palbociclib therapy and at the beginning of each cycle, as
well as on Day 14 of the first 2 cycles, and as clinically indicated.
When scheduling Day 14 monitoring and subsequent follow-up visits, remember to consider when the patient actually
receives her medication and initiates each cycle.
Detecting and Managing Neutropenia
• Neutropenia was the most frequently reported adverse event in both PALOMA-1 (75%) .
Grade ≥3 neutropenia was reported in 48% of patients receiving Palbociclib + letrozole in
PALOMA-1
• Dose interruption, dose reduction, or delay in starting treatment cycles is recommended
for patients who develop Grade 3 or 4 neutropenia1
• Advise patients to immediately report any signs or symptoms of myelosuppression or
infection, such as fever, chills, dizziness, shortness of breath, weakness, or any increased
tendency to bleed and/or to bruise1
• Primary prophylactic use of granulocyte-colony stimulating factors was not permitted in
PALOMA-1 , but they could be used to treat treatmentemergent neutropenia, as
indicated by the current American Society of Clinical Oncology guidelines2,3
CBC=complete blood count.
1. Palbociclib Prescribing Information.. 2. Data on file. Clinical Study Report: Protocol A5481003. New York, NY: Pfizer Inc; 2014. 3. Data on file. Clinical Study
Report: Protocol A5481023. New York, NY: Pfizer Inc; 2015.
52. Modify the Dose If Needed Based on Individual Safety
and Tolerability1
53
Recommended dose modifications for Palbociclib
Starting dose First reduction Second reduction
125 mg/day 100 mg/day 75 mg/day
If dose reduction below 75 mg/day is required, discontinue
1. IBRANCE® Prescribing Information. New York, NY: Pfizer Inc; 2016.
• Dose modifications may help manage hematologic and nonhematologic toxicities,
if they occur